Key words Behçet's disease · HLA-B51 · Neuro-Behçet's syndrome · SmokingCentral nervous system (CNS) involvement in Behçet's disease (BD) (neuro-Behçet's syndrome; NB) is usually lifethreatening, and requires aggressive therapy. 1,2 The most common manifestation of NB includes cranial nerve palsy, dysarthria, pyramidal tract signs, and ataxia with or without consciousness disturbances. 3 Recent studies have disclosed that NB can be classifi ed into acute type and chronic progressive type according to the clinical course. 4 Acute type NB is usually self-limiting, and responds to corticosteroid therapy, although recurrence sometimes takes place. By contrast, the chronic progressive type is characterized by intractable, slowly progressive neurobehavioral changes, ataxia, and dysarthria. 1,4 Of note, patients with the chronic progressive NB show persistent marked elevation of cerebrospinal fl uid (CSF) interleukin (IL)-6 despite of the very modest increase in cell numbers and total proteins. 4 Since most patients with the chronic progressive NB presented preceding episodes of the acute type attacks, it is suggested that persistence of some immune reaction within the CNS might play a pivotal role in the development of the chronic progressive neurological damage. 5 Here we explore risk factors for chronic progressive NB.A total of 150 patients with BD, who visited the clinic or were admitted to the hospital in Teikyo University School of Medicine between 2003 and 2005, were examined for HLA-B51 and habits of cigarette smoking. All 150 patients satisfi ed the International Study Group criteria for BD 6 (74 men, age 55.6 ± 13.1 years [mean ± SD]; 76 women, age 59.9 ± 14.6 years). We defi ned chronic progressive NB when the patients satisfi ed both of the following: the presence of slowly progressive neurobehavioral changes, ataxia, and dysarthria which persist for at least 1 year despite conventional treatment with corticosteroids, cyclophosphamide, azathioprine, and colchicine, and the persistent elevation of CSF IL-6 to more than 20 pg/ml for at least 1 year without any other conditions leading to the elevation of CSF IL-6. Seventeen patients of the 150 had been diagnosed as chronic progressive NB (13 men and 4 women) (P = 0.0208). In these 17 patients, HLA-B51 was positive in 16 patients (P < 0.001) and habitual cigarette smoking with Brinkman index more than 200 was confi rmed in 16 patients (P < 0.001) (Table 1). Moreover, 15 of the 17 patients with chronic progressive NB had both HLA-B51 and cigarette smoking habits, compared with 21 of the 133 patients without chronic progressive NB (P < 0.001). In male patients, the frequency of HLA-B51, habitual cigarette smoking, or both, was also signifi cantly higher in chronic progressive NB. Ten of the 133 patients without chronic progressive NB had presented self-limiting attacks of acute NB without any progressive CNS manifestations. We next compared the demographic features of these 10 patients with acute NB without progression with those of the 17 patients with chronic ...
